Tuneable Recombinant Spider Silk Protein Hydrogels for Drug Release and 3D Cell Culture

Author:

Arndt Tina1ORCID,Chatterjee Urmimala1ORCID,Shilkova Olga1ORCID,Francis Juanita1,Lundkvist Johan2,Johansson Daniel3,Schmuck Benjamin14,Greco Gabriele4ORCID,Nordberg Åsa Ekblad5,Li Yan6,Wahlberg Lars U2,Langton Maud3,Johansson Jan1,Götherström Cecilia5,Rising Anna14ORCID

Affiliation:

1. Department of Biosciences and Nutrition Karolinska Institutet Neo Huddinge 14152 Sweden

2. Sinfonia Biotherapeutics Hälsovägen 7 Huddinge 14157 Sweden

3. Department of Molecular Sciences Swedish University of Agricultural Sciences Uppsala 75007 Sweden

4. Department of Anatomy Physiology and Biochemistry Swedish University of Agricultural Sciences Uppsala 75007 Sweden

5. Department of Clinical Science Intervention and Technology Division of Obstetrics and Gynecology Karolinska Institutet Huddinge 14152 Sweden

6. Department of Clinical Science Intervention and Technology Division of Orthopedics and Biotechnology Karolinska Universitetssjukhuset Huddinge 141 86 Sweden

Abstract

AbstractHydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by‐products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non‐toxic, xeno‐free, and has good mechanical properties. A recombinant spider silk protein‐derived hydrogel that rapidly forms at 37 °C is recently developed. The temperature and gelation times are well‐suited for an injectable in situ polymerising hydrogel, as well as a 3D cell culture scaffold. Here, it is shown that the diffusion rate and the mechanical properties can be tuned by changing the protein concentration and that human fetal mesenchymal stem cells encapsulated in the hydrogels show high survival and viability. Furthermore, mixtures of recombinant spider silk proteins and green fluorescent protein (GFP) form gels from which functional GFP is gradually released, indicating that bioactive molecules are easily included in the gels, maintain activity and can diffuse through the gel. Interestingly, encapsulated ARPE‐19 cells are viable and continuously produce the growth factor progranulin, which is detected in the cell culture medium over the study period of 31 days.

Funder

European Research Council

Vetenskapsrådet

Publisher

Wiley

Subject

Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials

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